The anthracycline antibiotics (daunorubicin and doxorubicin) also do this

Cisplatin, carboplatin

Platinum coordination complexes

Cross-link DNA at any part of the cell cycle

Great for use in various combination regimens, but especially for ovarian and testicular cancer

Toxicity: Nephrotoxicity (due to hydration?), and acoustc nerve dysfunction causing tinnitis, or ringing in the ears

Resistance: DNA repair still occurs

Kidney: Site of extretion/metabolism/inactivation

Tamoxifen

Anti-tumor hormone partial agonist

Acts as a competitive inhibitor of estrogen by binding to the estrogen receptor

This is called a selective estrogen response modulator (SERM)

Toxicity: Little; manageable, such as hot flashes

Used in cancers of estrogen-responsive tissues: female and male breast (40% are ER+) and uterine endometrium

Also used as a prophylactic treatment to prevent breast cancer for high-risk women, but it hasn't been shown to significantly increase lifespan; it has been shown to reduce risks of bone fractures in postmenopausal women (just like postmenopausal estrogen replacement therapy)

Remember, a partial agonist is an effective antagonist because it causes a decreased effect of the original hormone binding the receptor

Raloxifene

Anti-tumor hormone targeting agent

SERM: Selective estrogen response modulator

Used for prevention of breast cancer in patients with osteoporosis

Has lower risks of endometrial cancer and thrombotic events than tamoxifen by the Study of Tamoxifen And Raloxifene (STAR) study

Letrozole, anastrozole, and exemestane

Aromatase inhibitors

Block conversion of androgens to estrogen in postmenopausal women

Not used in premenopausal women because of compensatory gonadotropin and ovarian estrogen production (feedback causes increased estrogen production from these sites)

More effective than tamoxifen for ER+ breast cancers in postmenopausal women

Exemestane: Also used as prophylaxis in high-risk postmenopausal women

Toxicity: No enhanced incidence of thrombosis or uterine cancer (contrasted to SERMs); joint pain and loss of bone density occur

Leuprolide

Anti-androgen therapyfor cancer

Synthetic peptide analog of GnRH that is a GnRH receptor agonist (this doesn't make sense to me)

If we give pulsatile infusions, then we end up getting elevated levels of androgens in men and estrogens in women

In Parkinson's disease, the loss of the nigrostriatal dopamine neurons results in increased firing of striatal cholinergic interneurons and overstimulation of muscarinic receptors; these drugs block that firing

Used for lithium-induced nephrogenic diabetes insipidus by blocking uptake of lithium by Na channels in the collecting duct

Spironolactone, eplerenone

Mineralocorticoid antagonists

Antagonize effects of ADH in distal convoluted tubule/collecting tubule, which results in increased secretion of sodium and chloride only

Efficacy depends upon how much water retention is due to ADH

These are the only diuretics that exert their influence from the "blood side"

Potassium sparing

Used for potassium sparing action, treatment of hyperaldosteronism, and treatment of ascites and edema with cirrhosis

Adverse effects: Hyperkalemia; there is some cross-reactivity with other steroid receptors, and can cause feminization or menstrual irregularities; diarrhea, gastritis, gastric bleeding, rash, CNS symptoms